Oligonucleotides conjugated to polymers are known. Further, the delivery of oligonucleotides conjugated to polymers (polyconjugates) for therapeutic purposes is also known. See WO2000/34343; WO2008/022309; and Rozema et al. PNAS (2008) 104, 32: 12982-12987.
Poly(amido amine) polymers are known. Z. Khayat et al. International Journal of Pharmaceutics (2006) 317:175-186; P. Ferruti et al. Macromol. Rapid Commun. (2002) 23:332-355; and Ka-Wai Wan et al. Biomacromolecules (2004) 5:1102-1109.
Polyconjugates have numerous toxicities associated with it as an oligonucleotide delivery vehicle. It is thus an object of the invention to provide polyconjugates that are biodegradable. Further, it is also an object of the invention to provide polyconjugates designed with components to increase liver uptake. Further, it is also an object of the instant invention to provide polyconjugates designed with components that facilitate oligonucleotide escape from the endosome. Herein, we disclose and describe novel membrane lytic poly(amido amine) polymers and polyconjugates useful for the delivery of oligonucleotides for therapeutic purposes.